T cell factor 1: A master regulator of the T cell response in disease
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This review discusses TCF1, which plays context-dependent roles in T cell function during autoimmunity, cancer, and chronic infection.
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TCF1 is a transcription factor critical for T cell memory, longevity and self-renewal.
“TCF1 is a transcription factor critical for T cell memory, longevity and self-renewal13.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [13]
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BackgroundInfluentialAn intra-tumoral niche maintains and differentiates stem-like CD8 T cells
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“However, a second study in tumors showed that bulk tumorspecific (Tag-I) CD8+ T cells, harvested early after tumor injection (and likely containing a higher portion of TCF1+ cells), could instead differentiate into functional memory cells when transferred into secondary hosts immunized with Listeria monocytogenes expr…”
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Self-citationThe TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness
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“Accordingly, deletion of Prdm1 was shown to promote the expansion of stem-like TCF1+ CD8+ T cells in the context of chronic viral infections (50, 52, 54).”
BackgroundResultInfluentialIL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.
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The dichotomous nature of T helper 17 cells
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“Last, none of the above studies addressed the role of TCF1 in regulating proinflammatory (pathogenic) versus homeostatic (non-pathogenic) TH17 subtypes (35, 36), which could have important implications for autoimmunity.”
BackgroundBrummelman, J., Mazza, E. M. C., Alvisi, G., Colombo, F. S., Grilli, A., Mikulak, J., Mavilio, D., Alloisio, M., Ferrari, F., Lopci, E., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180684 · Cited by 334 · see citing works
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Superior T memory stem cell persistence supports long-lived T cell memory.
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Early precursor T cells establish and propagate T cell exhaustion in chronic infection
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T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion
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PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity
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Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer
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Critical Involvement of Tcf-1 in Expansion of Thymocytes
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Differentiation of CD8 memory T cells depends on Foxo1
Michelini, R. H., Doedens, A. L., Goldrath, A. W., & Hedrick, S. Μ. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20130392 · Cited by 228 · cited 1× · see citing works
“FOXO1, which regulates T cell stemness and memory formation (86), is required for the expression of TCF1 (87) and is essential for the generation and maintenance of TCF1+ precursor T cells in chronic viral infection models (88).”
BackgroundLineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells
Johnson, J. L., Georgakilas, G., Petrovic, J., Kurachi, M., Cai, S., Harly, C., Pear, W. S., Bhandoola, A., Wherry, E. J., & Vahedi, G. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.012 · Cited by 226 · see citing works
Tcf1 and Lef1 transcription factors establish CD8+ T cell identity through intrinsic HDAC activity
Xing, S., Li, F., Zeng, Z., Zhao, Y., Yu, S., Shan, Q., Li, Y., Phillips, F. C., Maina, P. K., Qi, H. H., et al. (2016) · Nature Immunology · doi:10.1038/ni.3456 · Cited by 226 · see citing works
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Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity
Burkett, P. R., zu Hörste, G. M., & Kuchroo, V. K. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78085 · Cited by 221 · cited 4× · see citing works
“Moreover, autoimmune disorders such as multiple sclerosis (MS), psoriasis, type 1 diabetes (T1D), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) have steadily increased over the past four decades (14).”
BackgroundInfluentialMetabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity
Karmaus, P. W. F., Chen, X., Lim, S. A., Herrada, A. A., Nguyen, T.-L. M., Xu, B., Dhungana, Y., Rankin, S., Chen, W., Rosencrance, C., et al. (2019) · Nature · doi:10.1038/s41586-018-0806-7 · Cited by 215 · see citing works
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“However, enforced expression of ICAT, which specifically inhibits the interaction between -catenin and TCF1, did not affect IFN production by CD4+ T cells (25).”
BackgroundJadhav, R., Im, S., Hu, B., Hashimoto, M., Li, P., Lin, J., Leonard, W., Greenleaf, W., Ahmed, R., & Goronzy, J. (2019) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1903520116 · Cited by 203 · cited 1× · see citing works
“Role of TCF1 in the cross-talk between stem-like CD8+ T cells and other immune cells Epigenetic profiling of TCF1+ stem-like versus dysfunctional CD8+ T cells in chronic viral models revealed open chromatin regions at genes relevant for T cell–dendritic cell (DC) interactions such as XCL1 (104), which promotes the rec…”
BackgroundThe transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity
Gautam, S., Fioravanti, J., Zhu, W., Gall, J. B. L., Brohawn, P. Z., Lacey, N. E., Hu, J., Hocker, J. D., Hawk, N. V., Kapoor, V., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0311-z · Cited by 180 · see citing works
The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns
Oestreich, K., Huang, A. C., & Weinmann, A. S. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102144 · Cited by 168 · cited 1× · see citing works
“Subsequently, it was demonstrated that T-BET can recruit the transcriptional repressor BCL6 to the Tcf7 promoter and inhibit its gene expression (26).”
BackgroundTCF1 Is Required for the T Follicular Helper Cell Response to Viral Infection
Wu, T., Shin, H. M., Moseman, E. A., Ji, Y., Huang, B., Harly, C., Sen, J. M., Berg, L. J., Gattinoni, L., McGavern, D. B., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.049 · Cited by 167 · cited 1× · see citing works
“TCF1 has been demonstrated to have a critical role in the ability of TFH to support B cell activation and antibody production during viral infection (18, 19).”
BackgroundPetrovas, C., Ferrando-Martínez, S., Gerner, M. Y., Casazza, J., Pegu, A., Deleage, C., Cooper, A., Hataye, J., Andrews, S., Ambrozak, D. R., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aag2285 · Cited by 162 · cited 1×
“Similar to TFH cells, stem-like CD8+ T cells in chronic lymphocytic choriomeningitis virus (LCMV), human immunodeficiency virus (HIV), and simian immunodeficiency virus (SIV) infection models infiltrate B cell follicles (51, 52, 74) and are characterized by the expression of CXCR5, a well-known marker of TFH cells (50…”
Keerthivasan, S., Aghajani, K., Dose, M., Molinero, L. L., Khan, M. W., Venkateswaran, V., Weber, C. R., Emmanuel, A. O., Sun, T., Bentrem, D. J., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007607 · Cited by 161 · cited 2× · see citing works
“3 of 12 in both wild-type (CD4Cre) and CD4Cre-Ctnnb1ex3 CD4+ T cells, accessible chromatin regions marked by lysine acetylation of histone 3 (H3KAc) were found only in the presence of constitutively active -catenin signaling (30).”
BackgroundShan, Q., Zeng, Z., Xing, S., Li, F., Hartwig, S. M., Gullicksrud, J. A., Kurup, S. P., Budimir, N., Yao, S., Martin, M. D., et al. (2017) · Nature Immunology · doi:10.1038/ni.3773 · Cited by 157 · cited 1× · see citing works
“Runx3-deficient CD8+ T cells showed increased expression of Bcl6 and Tcf7 and subsequent reduction in the expression of cytotoxic molecules in effector T cells (93).”
BackgroundSuppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell Differentiation.
Danilo, M., Chennupati, V., Silva, J. G., Siegert, S., & Held, W. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.072 · Cited by 142 · cited 4× · see citing works
“TCF1 maintains T cell stemness by directly inhibiting Prdm1 (PR domain zinc finger protein 1) expression and allowing the transcription of memory-related genes such as Ccr7, IL7ra, Sell, and Cxcr5 that are otherwise repressed by Prdm1.”
BackgroundInfluentialSnell, L. M., MacLeod, B. L., Law, J. C., Osokine, I., Elsaesser, H. J., Hezaveh, K., Dickson, R. J., Gavin, M. A., Guidos, C. J., McGaha, T. L., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.08.002 · Cited by 119 · see citing works
Tcf1 and Lef1 are required for the immunosuppressive function of regulatory T cells
Xing, S.-J., Gai, K., Li, X., Shao, P., Zeng, Z., Zhao, X.-D., Zhao, X., Chen, X., Paradee, W., Meyerholz, D., et al. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20182010 · Cited by 101 · cited 2× · see citing works
“Treg-specific ablation of TCF1 and LEF1 did not affect Treg number but led to spontaneous multiorgan autoimmunity due both to the inability to maintain suppressive activity and to reduced survival downstream of impaired IL-2–STAT5 (signal transducer and activator of transcription 5) signaling (46, 47).”
BackgroundCD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions
Nish, S. A., Zens, K. D., Kratchmarov, R., Lin, W.-H. W., Adams, W. C. T., Chen, Y.-H., Yen, B., Rothman, N. J., Bhandoola, A., Xue, H., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20161046 · Cited by 100 · cited 1× · see citing works
“A recent paper on CD4+ T cells also suggested that asymmetric cell division drives the fate of CD4+ T cells (82).”
BackgroundTCR Signaling in T Cell Memory
Daniels, M., & Teixeiro, E. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00617 · Cited by 98 · see citing works
TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases
Yang, B.-H., Wang, K., Wan, S., Liang, Y., Yuan, X., Dong, Y., Cho, S., Xu, W.-Q., Jepsen, K., Feng, G.-S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.061 · Cited by 96 · cited 1× · see citing works
“Treg-specific ablation of TCF1 and LEF1 did not affect Treg number but led to spontaneous multiorgan autoimmunity due both to the inability to maintain suppressive activity and to reduced survival downstream of impaired IL-2–STAT5 (signal transducer and activator of transcription 5) signaling (46, 47).”
BackgroundControl of Lymphocyte Fate, Infection, and Tumor Immunity by TCF-1.
Raghu, D., Xue, H.-H., & Mielke, L. (2019) · Trends in immunology · doi:10.1016/j.it.2019.10.006 · Cited by 95 · cited 2× · see citing works
“In mature T cells, TCF1 is known to be critical for the generation of the CD8+ T cell memory response (5).”
BackgroundUtzschneider, D. T., Delpoux, A., Wieland, D., Huang, X., Lai, C.-Y., Hofmann, M., Thimme, R., & Hedrick, S. Μ. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.020 · Cited by 92 · cited 1× · see citing works
“FOXO1, which regulates T cell stemness and memory formation (86), is required for the expression of TCF1 (87) and is essential for the generation and maintenance of TCF1+ precursor T cells in chronic viral infection models (88).”
BackgroundQiang, S., Hu, S., Chen, X., Danahy, D. B., Badovinac, V., Zang, C., & Xue, H.-H. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-0436-5 · Cited by 86 · cited 2× · see citing works
“It is noteworthy that TCF1+ stem-like CD8+ T cells are enriched for interferon-stimulated genes (ISGs) (62) and that overexpression of the TCF1 long isoform in CD8+ T cells further increased ISG expression (84).”
BackgroundWang, Y.-F., Hu, J., Li, Y.-D., Xiao, M., Wang, H.-Q., Tian, Q., Li, Z.-R., Tang, J.-F., Hu, L., Tan, Y., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00169 · Cited by 79 · cited 1× · see citing works
“Conversely, overexpression of TCF1 can promote the formation of TCF1+ (CXCR5+ or SLAMF6+) stem-like precursor CD8+ T cells in the contexts of chronic viral infection and cancer (54, 73, 84, 85).”
BackgroundBrucklacher-Waldert, V., Ferreira, C., Stebegg, M., Fesneau, O., Innocentin, S., Marie, J. C., & Veldhoen, M. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.052 · Cited by 77 · cited 1× · see citing works
“Furthermore, the observed Wnt pathway–mediated inhibition of TH17 differentiation was suggested to involve repression of the transforming growth factor (TGF) pathway, which is important for the generation of both human and murine TH17 cells, although TH17 cells can differentiate in the absence of TGF, particularly…”
BackgroundYu, Q., Sharma, A., Ghosh, A., & Sen, J. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1003497 · Cited by 71 · cited 6× · see citing works
“Role in TH17 differentiation, plasticity, and stem-like phenotype Initial evidence for a role for TCF1 in TH17 biology came from studies using Tcf7 germline KO mice, showing that T cells in these mice had higher propensity to produce IL-17A and, consequently, exhibited exacerbated EAE (28, 29).”
BackgroundInfluentialGullicksrud, J. A., Li, F.-Y., Xing, S.-J., Zeng, Z., Peng, W.-Q., Badovinac, V., Harty, J., & Xue, H.-H. (2017) · Journal of Immunology · doi:10.4049/jimmunol.1700595 · Cited by 65 · cited 2× · see citing works
“Last, in a model of acute viral infection, long isoforms were dispensable in CD8+ T cells during the effector phase, but necessary for optimal generation of the memory CD8+ T cell pool (9).”
BackgroundT Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development.
Wu, J., Madi, A., Mieg, A., Hotz-Wagenblatt, A., Weisshaar, N., Ma, S., Mohr, K., Schlimbach, T., Hering, M., Borgers, H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.048 · Cited by 60 · cited 1× · see citing works
“In line with this, a recent report revealed that TCF1 expression prevents the acquisition of a TRM phenotype in CD8+ T cells by antagonizing TGF-induced CD103 expression in a lung infection model (94), suggesting that RUNX3 and TCF1 may antagonize each other.”
BackgroundMolecular dissection of CD8+ T cell dysfunction
Wang, C., Singer, M., & Anderson, A. (2017) · Trends in immunology · doi:10.1016/j.it.2017.05.008 · Cited by 57 · cited 2× · see citing works
“Late dysfunctional T cells, also referred to as “terminally exhausted” cells, are characterized by decreased effector functions, limited cytotoxic capacity, and high expression of several checkpoint receptors such as programmed cell death protein 1 (PD1), 2B4, T cell immunoglobulin mucin receptor 3 (TIM3), lymphocyte…”
BackgroundSelf-citationCritical Role of TCF-1 in Repression of the IL-17 Gene
Ma, J., Wang, R., Fang, X., Ding, Y. P., & Sun, Z. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024768 · Cited by 53 · cited 6× · see citing works
“Role in TH17 differentiation, plasticity, and stem-like phenotype Initial evidence for a role for TCF1 in TH17 biology came from studies using Tcf7 germline KO mice, showing that T cells in these mice had higher propensity to produce IL-17A and, consequently, exhibited exacerbated EAE (28, 29).”
BackgroundInfluentialThe Role of WNT Signaling in Mature T Cells: T Cell Factor Is Coming Home
van Loosdregt, J., & Coffer, P. J. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800633 · Cited by 50 · see citing works
TCF-1 Regulates Thymocyte Survival via a RORγt-dependent Pathway
Wang, R., Xie, H.-M., Huang, Z.-F., Ma, J., Fang, X.-F., Ding, Y., & Sun, Z.-M. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1101205 · Cited by 46 · cited 1× · see citing works
“This finding is in line with another report showing that TCF1 regulates the survival of double-positive thymocytes by augmenting RORT expression (31).”
ResultThe Wnt inhibitor secreted Frizzled‐Related Protein 1 (sFRP1) promotes human Th17 differentiation
Lee, Y., Lee, K.-A., Yoon, H., Yoo, S., Park, Y. W., Chung, Y., Kim, W.-U., & Kang, C.-Y. (2012) · European Journal of Immunology · doi:10.1002/eji.201242445 · Cited by 44 · cited 1× · see citing works
“In line with studies showing TCF1-mediated inhibition of IL-17A production in murine TH17 cells, in vitro studies of human CD4+ T cells showed that TH17 differentiation was enhanced by the presence of Wnt pathway inhibitors, such as secreted Fzd-related protein-1 (sFRP1), dickkopf-related protein 1 (DKK-1), and Wnt in…”
BackgroundA polymorphism in the TCF7 gene, C883A, is associated with type 1 diabetes.
Noble, J., White, A. M., Lazzeroni, L., Valdés, A., Mirel, D., Reynolds, R., Grupe, A., Aud, D., Peltz, G., & Erlich, H. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1579 · Cited by 44 · see citing works
Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus
Barra, M. M., Richards, D., Hansson, J., Hofer, A., Delacher, M., Hettinger, J. C., Krijgsveld, J., & Feuerer, M. (2015) · Journal of Immunology · doi:10.4049/jimmunol.1500821 · Cited by 41 · see citing works
Defining the functional states of Th17 cells
Lee, Y., & Kuchroo, V. K. (2015) · F1000Research · doi:10.12688/f1000research.6116.1 · Cited by 31 · cited 1× · see citing works
“Last, none of the above studies addressed the role of TCF1 in regulating proinflammatory (pathogenic) versus homeostatic (non-pathogenic) TH17 subtypes (35, 36), which could have important implications for autoimmunity.”
BackgroundZanon, V., Pilipow, K., Scamardella, E., Paoli, F. D., Simone, G. D., Price, D., Martinez-Usatorre, A., Romero, P., Mavilio, D., Roberto, A., et al. (2017) · European Journal of Immunology · doi:10.1002/eji.201646732 · Cited by 28 · see citing works
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The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2
Eugster (1998) · Pure Amsterdam UMC · doi:10.1002/(sici)1521-4141(199807)28:07 · Cited by 2 · see citing works
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CD8+ T cell differentiation and dysfunction in cancer
Philip, M., & Schietinger, A. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00574-3 · Cited by 1,052 · see citing works
Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W., Hsu, J.-M., Cha, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21099-2 · Cited by 637 · see citing works
Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer
Jia, D., Wang, Q., Qi, Y., Jiang, Y., He, J., Lin, Y., Sun, Y., Xu, J., Chen, W., Fan, L., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.022 · Cited by 479 · see citing works
CD8+ T Cell Exhaustion in Cancer
Dolina, J. S., Budimir, N., Thomas, G. D., & Salek‐Ardakani, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.715234 · Cited by 487 · see citing works
Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer
Bao, M. H.-R., & Wong, C. C.-L. (2021) · Cells · doi:10.3390/cells10071715 · Cited by 316 · see citing works
“Recently, exhausted T cells were further categorized into progenitor exhausted T cells and terminally exhausted T cells, as defined as PD1+TIM3-TCF1+ and PD1+TIM3+TCF1- T cells respectively [71].”
BackgroundLAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation
Joller, N., Anderson, A. C., & Kuchroo, V. K. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.010 · Cited by 287 · see citing works
Self-citationStem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Schnell, A., Huang, L., Singer, M., Singaraju, A., Barilla, R. M., Regan, B. M. L., Bollhagen, A., Thakore, P. I., Dionne, D., Delorey, T. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.018 · Cited by 268 · see citing works
An autoimmune stem-like CD8 T cell population drives type 1 diabetes
Gearty, S. V., Dündar, F., Zumbo, P., Espinosa-Carrasco, G., Shakiba, M., Sanchez-Rivera, F. J., Socci, N. D., Trivedi, P., Lowe, S. W., Lauer, P., et al. (2022) · Nature · doi:10.1038/s41586-021-04248-x · Cited by 257 · see citing works
CXCL9 and CXCL10 bring the heat to tumors
Reschke, R., & Gajewski, T. (2022) · Science immunology · doi:10.1126/sciimmunol.abq6509 · Cited by 192 · see citing works
“This led them to find that there was still a positive correlation between T cell factor 7+ (TCF7+) [a master regulator of T cell immunity involved in the generation of the CD8+ T cell memory (7)], T cells, and B cell accumulation, further strengthening the concept that T and B cell recruitment are intertwined via CXCL…”
BackgroundSignature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection
Adamo, S., Michler, J., Zurbuchen, Y., Cervia, C., Taeschler, P., Raeber, M. E., Sain, S. B., Nilsson, J., Moor, A., & Boyman, O. (2021) · Nature · doi:10.1038/s41586-021-04280-x · Cited by 141 · see citing works
Effector differentiation downstream of lineage commitment in ILC1 is driven by Hobit across tissues
Friedrich, C., Taggenbrock, R. L. R. E., Doucet-Ladevéze, R., Golda, G., Moenius, R., Arampatzi, P., Kragten, N., Kreymborg, K., de Agüero, M. D., Kastenmueller, W., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-01013-0 · Cited by 92 · see citing works
The diversity of CD8+ T cell dysfunction in cancer and viral infection
Galluzzi, L., Smith, K. N., Liston, A., & Garg, A. D. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01161-6 · Cited by 84 · see citing works
“Both human and mouse CD8 + T cells are indeed sensitive to apoptosis mediated by FAS as a terminal event in their life cycle 246,247 , which presumably represents another homeostatic mechanism to prevent unwarranted tissue damage 248 .”
Tumor immunogenicity dictates reliance on TCF1 in CD8+ T cells for response to immunotherapy
Escobar, G., Tooley, K., Oliveras, J. P., Huang, L., Cheng, H., Bookstaver, M. L., Edwards, C., Froimchuk, E., Xue, C., Mangani, D., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.08.001 · Cited by 89 · see citing works
Self-citationArchitects of immunity: How dendritic cells shape CD8 + T cell fate in cancer
Bhandarkar, V., Dinter, T., & Spranger, S. (2025) · Science Immunology · doi:10.1126/sciimmunol.adf4726 · Cited by 83 · see citing works
TCF-1: A maverick in T cell development and function
Gounari, F., & Khazaie, K. (2022) · Nature Immunology · doi:10.1038/s41590-022-01194-2 · Cited by 73 · see citing works
Borràs, D. M., Verbandt, S., Ausserhofer, M., Sturm, G., Lim, J., Verge, G. A., Vanmeerbeek, I., Laureano, R. S., Govaerts, J., Sprooten, J., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00605-4 · Cited by 67 · see citing works
“…PDCD1, LAG3, CTLA4, HAVCR2, ENTPD1, TCF7, TOX, EOMES, CXCL10, CXCL9, CXCL13, CXCR5, ICOS, IL18R1, IL15RA, IL18RAP, KLRG1, KLRK1, BCL6, SLAMF6 ) 40 (Supplementary Table S3), and critical cytokine or TCR signaling related components as well as transcription factors (TFs) upstream of…”
Wang, D.-K., Fang, J., Wen, S., Li, Q., Wang, J., Yang, L., Dai, W., Lu, H., Guo, J., Shan, Z., et al. (2022) · International Journal of Oral Science · doi:10.1038/s41368-022-00160-w · Cited by 67 · see citing works
Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models
Schoutrop, E., Poiret, T., Serafi, I. E., Zhao, Y. H., He, R., Moter, A., Henriksson, J., Hassan, M., Magalhaes, I., & Mattsson, J. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005691 · Cited by 60 · see citing works
Peña-Asensio, J., Calvo, H., Torralba, M., Miquel, J., Sanz-de-Villalobos, E., & Larrubia, J. (2021) · Cancers · doi:10.3390/cancers13081922 · Cited by 57 · see citing works
“The PD-1 level of the intrahepatic resident CD8+ cells inversely correlates with the expression of the transcription factor T-bet [72], which has been correlated with a late dysfunctional phenotype in the PD-1high pool, since the effector late dysfunctional pool expresses the transcription factor Eomes and loses T-bet…”
BackgroundInfluentialMarkowitz, G., Ban, Y., Tavarez, D. A., Yoffe, L., Podaza, E., He, Y., Martin, M. T., Crowley, M. J. P., Sandoval, T., Gao, D.-C., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01963-1 · Cited by 56 · see citing works
“TCF1 + progenitor-exhausted CD8 + T cells share key similarities with memory cells 13–16 and mediate more durable antitumor immunity than their TCF1 − effector-like counterparts 11,12,15,17 .”
Yuen, V. W., Chiu, D. K., Law, C., Cheu, J. W., Chan, C. Y., Wong, B. P., Goh, C.-C., Zhang, M. S., Xue, H. D. G., Tse, A. P., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.10.037 · Cited by 67 · see citing works
Tremain, A. C., Wallace, R. P., Lorentz, K., Thornley, T. B., Antane, J. T., Raczy, M. R., Reda, J. W., Alpar, A., Slezak, A. J., Watkins, E. A., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01086-2 · Cited by 50 · see citing works
miR-181a-regulated pathways in T-cell differentiation and aging
Kim, C., Ye, Z., Weyand, C. M., & Goronzy, J. J. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00240-1 · Cited by 54 · see citing works
Honardoost, M. A., Adinatha, A., Schmidt, F., Ranjan, B., Ghaeidamini, M., Rayan, N. A., Lim, M. G. L., Joanito, I., Lin, Q. X. X., Rajagopalan, D., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01300-z · Cited by 43 · see citing works
“…mediators TCF7 and LEF1 , which we identified as drivers of T/NK cell activation, are known to play a key role in maintenance of a Th17 stem-like population which can either give rise to effector Th17 cells or differentiate into highly tissue destructive Th17/Th1-like cells [10, 81, 102].”
BackgroundHighly multiplexed 3D profiling of cell states and immune niches in human tumors
Yapp, C., Nirmal, A. J., Zhou, F., Wong, A. Y. H., Tefft, J. B., Lu, Y. D., Shang, Z., Maliga, Z., Llopis, P. D. L. M. M., Murphy, G. F., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02824-x · Cited by 47 · see citing works
“Statistical significance observed between CD8 + T cells and Mast cells ( P = 0.0142) and macrophages and B cells ( P = 0.0068). d – f , The maximum intensity projections of a neutrophil showing marker subsets for identifying specific organelles ( d ), a multilobed nucleus ( e ) and the cytoskeleton ( f ). g , A 3D ren…”
InfluentialNeoadjuvant immunotherapy in mismatch-repair-proficient colon cancers
Tan, P. B., Verschoor, Y. L., van den Berg, J. G., Balduzzi, S., Kok, N. F. M., Ijsselsteijn, M. E., Moore, K., Jurdi, A. A., Tin, A., Kaptein, P., et al. (2025) · Nature · doi:10.1038/s41586-025-09679-4 · Cited by 34 · see citing works
“In addition, expression of TCF1 (encoded by TCF7 ), a marker of naive or stem-like T cells with proliferative potential 28 , was significantly higher in responders than in non-responders ( P = 0.0074).”
InfluentialZhu, L.-L., Zhou, X.-F., Gu, M.-D., Kim, J., Li, Y., Ko, C.-J., Xie, X.-P., Gao, T.-X., Cheng, X.-H., & Sun, S.-C. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00942-8 · Cited by 36 · see citing works
Learning from the nexus of autoimmunity and cancer
Mangani, D., Yang, D., & Anderson, A. C. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.022 · Cited by 33 · see citing works
Self-citationChen, Z., Zhu, Z., Hu, T., Yao, C., & Wu, T. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01378-4 · Cited by 36 · see citing works
“TCF1 – the “ identity ” of stemness TCF1, the most broadly reported pro-stem TF, has two major isoforms (short p33 and long p45) with distinct functions in different biological processes [101].”
Spatial determinants of CD8+ T cell differentiation in cancer
Tooley, K., Escobar, G., & Anderson, A. C. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.04.003 · Cited by 36 · see citing works
Self-citationMangani, D., Subramanian, A., Huang, L., Cheng, H., Krovi, S. H., Wu, Y., Yang, D., Moreira, T. G., Escobar, G., Schnell, A., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.09.017 · Cited by 35 · see citing works
Self-citationRevolutionizing tumor immunotherapy: unleashing the power of progenitor exhausted T cells
Fang, Z., Ding, X., Huang, H., Jiang, H.-W., Jiang, J.-T., & Zheng, X. (2024) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2024.0105 · Cited by 32 · see citing works
“Its role extends beyond the thymic development of T cells and encompasses the formation of the memory phenotype 24 .”
BackgroundRegulatory T cells constrain T cells of shared specificity to enforce tolerance during infection
Klawon, D., Pagane, N., Walker, M., Ganci, N. K., Miller, C. H., Gai, E., Rodriguez, D. M., Ryan-Payseur, B., Duncombe, R., Adams, E. J., et al. (2025) · Science · doi:10.1126/science.adk3248 · Cited by 31 · see citing works
Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet
Muñoz-Rojas, A., Wang, G., Benoist, C., & Mathis, D. (2024) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2320602121 · Cited by 31 · see citing works
“They are a perplexing population because they express many markers characteristic of naive T cells (37); yet they are found in tissues.”
The molecular consequences of androgen activity in the human breast
Raths, F., Karimzadeh, M., Ing, N., Martinez, A., Yang, Y., Qu, Y., Lee, T.-Y., Mulligan, B., Devkota, S., Tilley, W. T., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100272 · Cited by 36 · see citing works
Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control
Perdomo-Celis, F., Passaes, C., Monceaux, V., Volant, S., Boufassa, F., de Truchis, P., Marcou, M., Bourdic, K., Weiss, L., Jung, C., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci157549 · Cited by 40 · see citing works
“In part, the stem-like profile of memory CD8+ T cells is mediated by the transcription factor TCF-1, a downstream component of the Wnt/β-catenin pathway (11).”
Vanmeerbeek, I., Borràs, D., Sprooten, J., Bechter, O. E., Tejpar, S., & Garg, A. D. (2021) · Genes and Immunity · doi:10.1038/s41435-021-00138-4 · Cited by 28 · see citing works
“Next, we decided to benchmark the predictive efficacy of LECA-genes in a clinical trial involving melanoma patients (n= 41), wherein transcriptomic profiling of the tumours was done at baseline, i.e., before anti-PD1 ICBs monotherapy (nivolumab/pembrolizumab), relative to OS monitoring [42].”
BackgroundInfluentialPhenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes
Sun, Y.-K., Yinwang, E., Wang, S.-D., Wang, Z.-N., Wang, F., Xue, Y., Zhang, W., Zhao, S.-Z., Mou, H., Chen, S.-X., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02104-w · Cited by 27 · see citing works
“TCF1 is a well-known enactor of Wnt-β-catenin signals and assumes a myriad of roles in T cell development and maturation pending the precise circumstance [120, 121].”
BackgroundXiang, S., Li, S., & Xu, J. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70345 · Cited by 26 · see citing works
“98,99 Based on the expression of Tcf-1 (a TF that inhibits effector development), TIM-3 is a reliable indicator for Tex. 8,100 104 TIM-3 overexpression exacerbates tumour progression.”
Stem-like CD8+ T cells in cancer
Steiner, C., Denlinger, N., Huang, X.-P., & Yang, Y.-P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1426418 · Cited by 26 · see citing works
Dimitri, A. J., Baxter, A. E., Chen, G. M., Hopkins, C. R., Rouin, G. T., Huang, H., Kong, W., Holliday, C., Wiebking, V., Bartoszek, R. L., et al. (2024) · Science Advances · doi:10.1126/sciadv.adp9371 · Cited by 37 · see citing works
“High IR expression and decreased expression of the transcription factor (TF) T cell factor 1 (TCF1) is associated with terminal differentiation of CD8 + T cells ( 21 ).”
Wang, X.-R., Lu, L., Hong, X., Wu, L.-L., Yang, C., Wang, Y., Li, W., Yang, Y.-Q., Cao, D., Di, W., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113712 · Cited by 24 · see citing works
Inflammation-mediated fibroblast activation and immune dysregulation in collagen VII-deficient skin
Anderson-Crannage, M., Ascensión, A., Ibáñez-Solé, O., Zhu, H.-W., Schaefer, E., Ottomanelli, D., Hochberg, B., Pan, J., Luo, W., Tian, M., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1211505 · Cited by 24 · see citing works
“Tcf7 encodes T-cell factor-1 (TCF-1) that marks either naïve or central memory stem-like precursor CD8 T cells with self-renewal capacity (50).”
BackgroundQuon, S., Yu, B.-F., Russ, B. E., Tsyganov, K., Nguyen, H., Toma, C., Heeg, M., Hocker, J. D., Milner, J., Crotty, S., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.03.017 · Cited by 24 · see citing works
Yin, L., Zhou, S.-B., Zhang, H., Yao, C.-B., Al-Qadhi, Z., Shang, Y., Wu, S., & Jin, T. (2025) · Antibody Therapeutics · doi:10.1093/abt/tbaf017 · Cited by 23 · see citing works
Androgen receptor signaling in non-prostatic malignancies: challenges and opportunities
Dotto, G., Buckinx, A., Özdemir, B., & Simon, C. (2024) · Nature Reviews. Cancer · doi:10.1038/s41568-024-00772-w · Cited by 23 · see citing works
Tong, R., Luo, L., Zhao, Y., Sun, M., Li, R., Zhong, J., Chen, Y., Hu, L., Li, Z., Shi, J., et al. (2023) · Emerging Microbes & Infections · doi:10.1080/22221751.2023.2187245 · Cited by 21 · see citing works
“The DEG analysis showed that the expression of Th and memory T cell di ff erentiation transcription factor (TF) genes TCF7 [42], LEF1 [43], STAT1 [44], STAT5B [45] and IKZF1 [46] was upregulated in the 2V7 and 2V14 groups compared with BV group (Figure 5C and S5C).”
ResultSu, Y., Liu, J.-Q., Tian, Y., Dong, H., Shi, M., Zhang, J., Li, W.-Q., Huang, Q., Xiang, N., Wang, C., et al. (2024) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2024.116427 · Cited by 21 · see citing works
microRNAs: Critical Players during Helminth Infections
Rojas-Pirela, M., Andrade-Alviárez, D., Quiñones, W., Rojas, M., Castillo, C., Liempi, A., Medina, L., Guerrero-Muñoz, J., Fernández-Moya, A., Ortega, Y., et al. (2022) · Microorganisms · doi:10.3390/microorganisms11010061 · Cited by 21 · see citing works
Xie, L., Gong, J., He, Z., Zhang, W.-N., Wang, H.-Y., Wu, S., Wang, X.-X., Sun, P.-J., Cai, L., Wu, Z.-J., et al. (2025) · Small · doi:10.1002/smll.202412174 · Cited by 19 · see citing works
Zhou, T.-X., Hou, X., Yan, J.-R., Li, L., Xie, Y.-J., Bai, W., Jiang, W.-N., Zou, Y., Li, X., Liu, Z.-Y., et al. (2024) · Gut · doi:10.1136/gutjnl-2024-332371 · Cited by 19 · see citing works
Wu, M.-H., Valença-Pereira, F., Cendali, F., Giddings, E. L., Pham-Danis, C., Yarnell, M. C., Novak, A. J., Brunetti, T. M., Thompson, S. B., Henao-Mejia, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48653-y · Cited by 19 · see citing works
“…analyses also revealed higher expression of Tcf7 (encoding Tcf1 ), I fi tm3, Itgae (encoding CD103), and Sell (encoding CD62L) genes in MCJ KO CD8 CAR-T cells, all of which are involved in the generation or survival of central memory or tissue resident memory CD8 cells 84 – 87 (Supplementary Fig.”
Stem‐like T cells in cancer and autoimmunity
Schnell, A. (2024) · Immunological Reviews · doi:10.1111/imr.13356 · Cited by 22 · see citing works
“7 TCF1 induces the expression of BCL6 and together they suppress T-cell differentiation and maintain T-cell stemness.”
Yang, Y., Wang, Y., Wang, Z., Yan, H., Gong, Y., Hu, Y., Jiang, Y., Wen, S., Xu, F., Wang, B., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01351-9 · Cited by 16 · see citing works
“Note that the TCF-1-centred transcriptional network plays a master regulatory role in generating the CD8 + T cell memory response 11,18 .”
TCF-1 Is Required for CD4 T Cell Persistence Functions during AlloImmunity
Mammadli, M., Suo, L., Sen, J., & Karimi, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054326 · Cited by 18 · see citing works
“CD28 is a key co-stimulatory receptor that plays a central role in T cell receptor stemness [2,80].”
BackgroundInfluentialBravetti, G., Falvo, P., Talarico, G., Orecchioni, S., & Bertolini, F. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216441 · Cited by 15 · see citing works
Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1
Kim, J., Lee, H., Lee, J.-E., Choi, G., Chung, H., Kim, D., Park, M. J., Gye, Y., Shin, K.-S., Kang, C., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2213793120 · Cited by 17 · see citing works
“In addition, TCF-1 is known to be required for maintaining stemness of T cells and regulating exhaustion, particularly in CD8 + T cells (41).”
Horisberger, A., Griffith, A. M., Keegan, J., Arazi, A., Pulford, J. F., Murzin, E., Howard, K., Hancock, B. L., Fava, A., Sasaki, T., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci181034 · Cited by 26 · see citing works
“Interestingly, T12 (TCD4 naive) was distinguished from T2 (TCD4 naive) by its reduced expression of TCF1, a key transcription factor in T cell stemness that is downregulated upon effector T cell differentiation (48) (Supplemental Figure 6, B and C).”
Sun, L.-J., Ma, Z.-B., Zhao, X., Tan, X., Tu, Y., Wang, J.-Z., Chen, L., Chen, Z.-S., Chen, G., & Lan, P.-X. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008367 · Cited by 16 · see citing works
“28 In addition, these stem-like Tex cells exhibit a more potent proliferative and functional capacity in response to immuno-therapy.”
BackgroundKim, J., Bose, D., Araínga, M., Haque, M. R., Fennessey, C. M., Caddell, R. A., Thomas, Y., Ferrell, D. E., Ali, S. A., Grody, E. I., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45555-x · Cited by 14 · see citing works
“T cell activation leads to reduced levels of TCF1 and higher levelsof TCF1 are present in T cells with higher stemnessand lowanabolic metabolism 74 .”
Systematic, Protein Activity-based Characterization of Single Cell StatePreprint
Vlahos, L. J., Obradovic, A., Worley, J., Tan, X.-T., Howe, A., Laise, P., Wang, A. L. E., Drake, C. G., & Califano, A. (2021) · bioRxiv · doi:10.1101/2021.05.20.445002 · Cited by 16 · see citing works
Co-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness
Khopanlert, W., Choochuen, P., Maneechai, K., Jangphattananont, N., Ung, S., Okuno, S., Steinberger, P., Leitner, J., Sangkhathat, S., Viboonjuntra, P., et al. (2024) · Molecular therapy. Oncology · doi:10.1016/j.omton.2024.200837 · Cited by 15 · see citing works
“34 In addition, the activity of TCF-1 is inhibited by ID2 .”
Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer
Yu, Q.-X., Wang, J.-C., Liu, J., Ye, L.-X., Guo, Y.-Q., & Zheng, H.-H. (2023) · Scientific Reports · doi:10.1038/s41598-023-41992-8 · Cited by 15 · see citing works
“Jia Lv et al. reported that BC patients with higher infiltration levels of CD8 + T cell and lower Mast cells are more likely to present with better immunotherapeutic effect and prognosis 50–52 .”
BackgroundMechanism of Sex Differences in Bladder Cancer: Evident and Elusive Sex-biasing Factors
Lam, C. M., Li, Z.-H., Theodorescu, D., & Li, X. (2022) · Bladder Cancer · doi:10.3233/blc-211658 · Cited by 15 · see citing works
The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity
Jung, S., & Baek, J.-H. (2021) · Cancers · doi:10.3390/cancers13030515 · Cited by 15 · see citing works
Balasubramanian, P., Balaji, U., Santos, M. S., Baisch, J. M., Smitherman, C., Walters, L., Sparagana, P. R., Nassi, L., Stewart, K., Fuller, J., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02297-2 · Cited by 15 · see citing works
“High CCR7 , LEF1 and TCF7 and low S100A4 expression characterized the naive cluster, whereas the opposite pattern identified the memory cluster 12,13 (Fig.”
Denlinger, N., Song, N., Zhang, X., Jeon, H., Peterson, C. M., Wang, Y., Reynolds, K., Bolz, R. M., Miao, J., Song, C., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023012073 · Cited by 15 · see citing works
TCF-1 regulates NKG2D expression on CD8 T cells during anti-tumor responses
Harris, R. B., Mammadli, M., Hiner, S., Suo, L., Yang, Q., Sen, J., & Karimi, M. (2022) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-022-03323-0 · Cited by 13 · see citing works
“T Cell Factor-1 (TCF-1), a major T cell developmental transcription factor, is involved in the Wnt signaling pathway, and is critical for T cell development as well as activation [1, 2].”
BackgroundResultArnovitz, S., Mathur, P. S., Tracy, M., Mohsin, A., Mondal, S., Quandt, J., Hernandez, K., Khazaie, K., Dose, M., Emmanuel, A., et al. (2022) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2201493119 · Cited by 13 · see citing works
“Tcf-1, a member of the Tcf/Lef family of transcriptional regulators, plays critical roles at multiple stages of T cell development and function, including the DP stage investigated here (30, 48, 49).”
BackgroundYang, A.-R., Zhou, M., Gao, Y.-X., & Zhang, Y. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114843 · Cited by 12 · see citing works
The Role of Natural Killer Cells in Oncolytic Virotherapy: Friends or Foes?
Franks, M. L., An, J.-H., & Leavenworth, J. (2024) · Vaccines · doi:10.3390/vaccines12070721 · Cited by 12 · see citing works
PD-1 limits differentiation and plasticity of Tc17 cells
Arra, A., Lingel, H., Pierau, M., & Brunner-Weinzierl, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1104730 · Cited by 12 · see citing works
“In chronic infection models and tumor samples it has been demonstrated that, persistent progenitor exhausted TCF1 CD8 T-cells recall and give rise to cytotoxic short lived terminally exhausted TCF1 cells required for effective immunity against infections and cancers (61).”
Silva, D. N., Chrobok, M., Rovesti, G., Healy, K., Wagner, A., Maravelia, P., Gatto, F., Mazza, M., Mazzotti, L., Lohmann, V., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.896242 · Cited by 12 · see citing works
Supercharging CAR-T cells through transcriptional and epigenetic armoring
Qin, D., Lei, Y., Shu, P., Zhang, Y., Loh, Y., Wang, Y., & Li, Q. (2025) · Theranostics · doi:10.7150/thno.107908 · Cited by 12 · see citing works
“Interestingly, the TCF1 homolog LEF1 also has similar DNA-binding domains and HDAC activity sequences, positioning it as a critical TF closely associated with T cell development and differentiation [40, 52, 98].”
Genomic analysis of Foxp3 function in regulatory T cells
Dolsten, G. A., & Pritykin, Y. (2023) · Journal of Immunology · doi:10.4049/jimmunol.2200864 · Cited by 11 · see citing works
McKenzie, C., El-Kholy, M., Parekh, F., Robson, M., Lamb, K., Allen, C., Sillibourne, J., Cordoba, S.-P., Thomas, S., & Pule, M. (2023) · Molecular Therapy: Nucleic Acids · doi:10.1016/j.omtn.2023.04.017 · Cited by 11 · see citing works
“…to demonstrate an advantage over other Fas-TNFRs by enhancing CAR T cell proliferation and maintaining T cell memory, particularly in the context of a CD28-containing CAR, likely mediated by increased TCF-1 expression 23 and upregulation of FasL, potentially creating a feedforward activation loop.”
Rapier-Sharman, N., Clancy, J., & Pickett, B. (2022) · Journal of Bioinformatics and Systems Biology · doi:10.26502/jbsb.5107040 · Cited by 11 · see citing works
“If CTNNB1 is not degraded by AXIN1, CTNNB1 translocates to the nucleus and interacts with LEF1, which we found to be significantly upregulated, and TCF7 (not significant in this study), causing transcription of Wnt pathway target genes to occur [72, 73].”
BackgroundStem-like T cells and niches: Implications in human health and disease
Yi, L., & Li, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.907172 · Cited by 12 · see citing works
Li, G.-M., Lou, Y., Ma, J., Cheng, L., Yu, H.-S., Tsahouridis, O., He, X.-Y., Funaki, M., Ahodantin, J., Bi, W., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adr3930 · Cited by 10
Brodsky, N. N., Chakder, M., Kumar, D., Barmada, A., Wang, J., Gu, W.-H., Olaloye, O., Ramaswamy, A., Wats, A., Konnikova, L., et al. (2025) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2421106122 · Cited by 10 · see citing works
“Previous studies of activated mouse and human CD4 + T cells have demonstrated a similar pattern, indicating a quick shift toward effector - like cell differentiation and away from naïve - like and memory cell differentiation in both CD4 + and CD8 + T cells of neonates ( 13 , 53 , 54 ).”
Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma
Rosenberg, M. I., Greenstein, E., Buchkovich, M. L., Peres, A., Santoni-Rugiu, E., Yang, L., Mikl, M., Vaksman, Z., Gibbs, D., Reshef, D., et al. (2021) · bioRxiv · doi:10.1016/j.celrep.2023.112879 · Cited by 10 · see citing works
“Notably, OMAS-associated neuroblastoma showed significant increased differential expression of TCF7, a marker of stem-cell-like CD8 + T cells and regulator of autoimmunity, in both comparisons (Table S2 and Figure S1; reviewed in Escobar et al. 23 ).”
He, J., Burova, E., Taduriyasas, C., Ni, M., Adler, C., Wei, Y., Negron, N., Xiong, K., Bai, Y., Shavlakadze, T., et al. (2025) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2425992122 · Cited by 9 · see citing works
“S1 D and F ) ( 34 ).”
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“15,31 Indeed, total T cell numbers were reduced in the thymus, spleen, and LN of Tcf7 fl/fl VavCre mice compared to the Tcf7 fl/fl mice (Figures S3D–S3F).”
Pérez-Quintero, L.-A., Poirier, A., Feng, C.-H., Martinez-Cordova, Z., Aubry, I., Carli, C., Kamyabiazar, S., Pacis, A., Zolotarov, Y., Pike, K., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113610 · Cited by 8
“Progressive loss of PTPN1 alleles was also associated to a decrease in TFs related to T cell exhaustion, such as Klf2 , Tox , and Tcf7 (Figure 4).”
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Parkin activates innate immunity and promotes antitumor immune responses
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“In turn, Parkin-expressing cells released an IFN secretome that upregulated effector and cytotoxic CD8 + T cell markers, lowered the expression of immune inhibitory receptors TIM3 and LAG3, and stimulated high content of the self renewal/stem cell factor, TCF1.”
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“This, combined with the increased expression of TCF7 in Cluster 1, which encodes a transcription factor (TCF1) that is more highly expressed in naïve than in differentiated cells 39 , suggests that cells in Cluster 1 were less differentiated than those in Cluster 2.”
Signaling networks controlling ID and E protein activity in T cell differentiation and function
Hwang, S., Im, S., & Rudra, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.964581 · Cited by 11 · see citing works
High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion
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Latent EBV enhances the efficacy of anti-CD3 mAb in Type 1 diabetes
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“Therefore, some of the mechanistic connections that are already discussed by the authors should be interrogated with experimental data.”
Membrane-bound IL-15 co-expression powers a potent and persistent CD70-targeted TRuC T-cell therapy
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Bryant, N., Muehling, L., Wavell, K., Teague, W. G., & Woodfolk, J. A. (2025) · JCI Insight · doi:10.1172/jci.insight.189480 · Cited by 6 · see citing works
“…non-resident CD4 + Tem phenotypes were shared with those found in the blood, including Th17-like cells (CD69 – CD103 – CCR6 + CD161 + , clusters 31 and 32) that displayed increased stemness (TCF-1 + ) and were less activated (CD127 + ), perhaps reflecting recent egress from blood (50, 51).”
Ntostoglou, K., Theodorou, S. D. P., Proctor, T., Nikas, I., Awounvo, S., Sepsa, A., Georgoulias, V., Ryu, H. S., Pateras, I. S., & Kittas, C. (2024) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-024-03630-8 · Cited by 6 · see citing works
“TCF1 is expressed by progenitor T cells, while its expression is decreased in terminally exhausted T cells [13, 15].”
Background
- Authors
- Escobar, G., Mangani, D., & Anderson, A. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Escobar, Giulia
- Mangani, Davide
- Anderson, Ana C.
- Venue
- Science Immunology
- Published
- 2020-11-13
- Volume
- 5
- Issue
- 53
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC8221367
- OpenAlex
- W3096010551
- Cited by
- 211
- References
- 131
- Citations by year
- 2026: 38 · 2025: 50 · 2024: 51 · 2023: 31 · 2022: 26 · 2021: 15
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (183910)
- National Cancer Institute (R01CA187975)
- National Institute of Allergy and Infectious Diseases (P01AI073748)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- TCF1, T cell response regulation, peripheral T cells, autoimmunity, tumor immunology, chronic infection, inflammatory diseases, immune-targeted therapy, T cell development
- MeSH terms
- Animals, Autoimmune Diseases, Cell Communication, Cell Differentiation, Chronic Disease, Disease Models, Animal, Gene Expression Regulation, Humans, Immunologic Factors, Immunologic Memory, Neoplasms, T-Lymphocytes, Virus Diseases, Chromatin Assembly and Disassembly, T Cell Transcription Factor 1, Wnt Signaling Pathway
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